Transbronchial Lung Cryobiopsy for Interstitial Lung Disease Diagnosis: Results of the COLDICE Study

Abstract

Background: Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease (ILD) diagnosis. Despite its increasing use, the diagnostic accuracy of TBLC compared to surgical lung biopsy (SLB) remains unclear. Methods: We conducted a prospective, multicentre study investigating diagnostic agreement between TBLC and SLB. After screening at a centralised multi-disciplinary discussion (MDD), ILD patients referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Blinded analysis of biopsy samples was conducted by 3 pathologists, individually and by consensus. At subsequent MDD, deidentified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Primary endpoints were: 1) agreement of histopathological features in TBLC and SLB for patterns of definite/probable usual interstitial pneumonia (UIP), indeterminate for UIP and diagnosis; and for 2) agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and kappa values were calculated. Findings: 65 patients (31 males; age 66·1±9·3yrs; FVC 84·7±14·2%; DLCO 63·4±13·8%) were enrolled. TBLC (7·1±1·9mm) and SLB samples (46·5±14·9mm) were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8%, weighted κ 0·70 (95%CI 0·55-0·86); diagnostic agreement at MDD was 76·9%, κ 0·62 (95%CI 0·47-0·78). For TBLC with high/definite diagnostic confidence at MDD (39/65, 60% cases), 37 (94·9%) were concordant with SLB diagnoses. In the 26/65 (40.0%) with low-confidence/unclassifiable TBLC diagnoses, SLB reclassified only 6 (23.1%) to alternative high/definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (21.5%) patients due to TBLC. Interpretation: High agreement between TBLC and SLB for histopathological patterns and MDD diagnoses support the clinical utility of TBLC in ILD diagnostic algorithms. Trial Registration: Australian New Zealand Clinical Trials Registry http://www.anzctr.org.au/ study ID ACTRN12615000718549. Funding Statement: University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin GmbH, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss and Olympus. Declaration of Interests: LKT received study-related unrestricted educational grants or inkind support from the aforementioned commercial entities, on behalf of the COLDICE Investigator Team. TJC reports grants, personal fees and non-financial support from Boehringer Ingelheim, grants and personal fees from Roche, grants from Galapagos, grants from Actelion, grants from Bayer, outside the submitted work. MPV sits on the advisory boards of Medtronic and Edwards Lifesciences, and consults for Edwards Lifesciences and Abbott. GR provides consultation for Bellerophon, Biogen, BMS, FibroGen, Gilead, Nitto, Revistan, Promedior, Sanofi, Veracyte, Roche-Genentech, Avalyn and Boehringer Ingelheim. JM is an unpaid collaborator in the Veracyte BRAVE Trial. Ethics Approval Statement: Ethics approval of the trial protocol was provided by an independent ethics committee at each participating site. Both the steering committee and data and safety monitoring board provided trial oversight, including contemporaneous review of all safety events. Participants gave fully informed consent.